Bleau A M, Planque N, Lazar N, Zambelli D, Ori A, Quan T, Fisher G, Scotlandi K, Perbal B
Université Paris7-D. Diderot, UFR de Biochimie, Laboratoire d'Oncologie Virale et Moléculaire, 2 place Jussieu, 75005 Paris, France.
J Cell Biochem. 2007 Aug 15;101(6):1475-91. doi: 10.1002/jcb.21262.
Previous work had suggested that recombinant CCN3 was partially inhibiting cell proliferation. Here we show that native CCN3 protein secreted into the conditioned medium of glioma transfected cells indeed induces a reduction in cell proliferation. Large amounts of CCN3 are shown to accumulate both cytoplasmically and extracellularly as cells reach high density, therefore highlighting new aspects on how cell growth may be regulated by CCN proteins. Evidence is presented establishing that the amount of CCN3 secreted into cell culture medium is regulated by post-translational proteolysis. As a consequence, the production of CCN3 varies throughout the cell cycle and CCN3 accumulates at the G2/M transition of the cycle. We also show that CCN3-induced inhibition of cell growth can be partially reversed by specific antibodies raised against a C-terminal peptide of CCN3. The use of several clones expressing various portions of CCN3 established that the CT module of CCN3 is sufficient to induce cell growth inhibition.
先前的研究表明，重组CCN3可部分抑制细胞增殖。在此我们发现，胶质瘤转染细胞条件培养基中分泌的天然CCN3蛋白确实会导致细胞增殖减少。研究表明，随着细胞达到高密度，大量CCN3会在细胞质和细胞外积累，因此凸显了CCN蛋白调控细胞生长的新机制。有证据表明，分泌到细胞培养基中的CCN3量受翻译后蛋白水解作用调控。因此，CCN3的产生在整个细胞周期中有所不同，且在细胞周期的G2/M期积累。我们还发现，针对CCN3 C末端肽产生的特异性抗体可部分逆转CCN3诱导的细胞生长抑制。使用多个表达CCN3不同部分的克隆证实，CCN3的CT模块足以诱导细胞生长抑制。
